TY - JOUR
T1 - Functions of the cytoplasmic RNA sensors RIG-I and MDA-5
T2 - Key regulators of innate immunity
AU - Barral, Paola M.
AU - Sarkar, Devanand
AU - Su, Zao zhong
AU - Barber, Glen N.
AU - DeSalle, Rob
AU - Racaniello, Vincent R.
AU - Fisher, Paul B.
N1 - Funding Information:
The present studies were supported in part by the National Institutes of Health grants GM068448 (PBF), AI079336 (GNB) and AI50754 and AI068017 (VRR). Support was also provided by the Samuel Waxman Cancer Research Foundation (SWCRF) (PBF). RD thanks the Sackler Institute for Comparative Genomics, the Lewis and Dorothy B Cullman Program in Molecular Systematics and the Korein Family Foundation all at the American Museum of Natural History for their continued support. Support from the VCU Institute of Molecular Medicine to DS and PBF is acknowledged. DS is a Harrison Scholar in Cancer Research at the VCU Massey Cancer Center, VCU School of Medicine. PBF holds the Thelma Newmeyer Corman Chair in Cancer Research at the VCU Massey Cancer Center, VCU School of Medicine and is a SWCRF Investigator.
PY - 2009/11
Y1 - 2009/11
N2 - The innate immune system responds within minutes of infection to produce type I interferons and pro-inflammatory cytokines. Interferons induce the synthesis of cell proteins with antiviral activity, and also shape the adaptive immune response by priming T cells. Despite the discovery of interferons over 50 years ago, only recently have we begun to understand how cells sense the presence of a virus infection. Two families of pattern recognition receptors have been shown to distinguish unique molecules present in pathogens, such as bacterial and fungal cell wall components, viral RNA and DNA, and lipoproteins. The first family includes the membrane-bound toll-like receptors (TLRs). Studies of the signaling pathways that lead from pattern recognition to cytokine induction have revealed extensive and overlapping cascades that involve protein-protein interactions and phosphorylation, and culminate in activation of transcription proteins that control the transcription of genes encoding interferons and other cytokines. A second family of pattern recognition receptors has recently been identified, which comprises the cytoplasmic sensors of viral nucleic acids, including MDA-5, RIG-I, and LGP2. In this review we summarize the discovery of these cytoplasmic sensors, how they recognize nucleic acids, the signaling pathways leading to cytokine synthesis, and viral countermeasures that have evolved to antagonize the functions of these proteins. We also consider the function of these cytoplasmic sensors in apoptosis, development and differentiation, and diabetes.
AB - The innate immune system responds within minutes of infection to produce type I interferons and pro-inflammatory cytokines. Interferons induce the synthesis of cell proteins with antiviral activity, and also shape the adaptive immune response by priming T cells. Despite the discovery of interferons over 50 years ago, only recently have we begun to understand how cells sense the presence of a virus infection. Two families of pattern recognition receptors have been shown to distinguish unique molecules present in pathogens, such as bacterial and fungal cell wall components, viral RNA and DNA, and lipoproteins. The first family includes the membrane-bound toll-like receptors (TLRs). Studies of the signaling pathways that lead from pattern recognition to cytokine induction have revealed extensive and overlapping cascades that involve protein-protein interactions and phosphorylation, and culminate in activation of transcription proteins that control the transcription of genes encoding interferons and other cytokines. A second family of pattern recognition receptors has recently been identified, which comprises the cytoplasmic sensors of viral nucleic acids, including MDA-5, RIG-I, and LGP2. In this review we summarize the discovery of these cytoplasmic sensors, how they recognize nucleic acids, the signaling pathways leading to cytokine synthesis, and viral countermeasures that have evolved to antagonize the functions of these proteins. We also consider the function of these cytoplasmic sensors in apoptosis, development and differentiation, and diabetes.
KW - Antiviral innate immunity
KW - Apoptosis
KW - Cell signaling
KW - Domain grafting
KW - MDA-5
KW - RIG-I
KW - Viral pathogenesis
UR - http://www.scopus.com/inward/record.url?scp=70349139611&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349139611&partnerID=8YFLogxK
U2 - 10.1016/j.pharmthera.2009.06.012
DO - 10.1016/j.pharmthera.2009.06.012
M3 - Review article
C2 - 19615405
AN - SCOPUS:70349139611
VL - 124
SP - 219
EP - 234
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
SN - 0163-7258
IS - 2
ER -